PMID- 15310764
OWN - NLM
STAT- MEDLINE
DCOM- 20041115
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 279
IP  - 40
DP  - 2004 Oct 1
TI  - Hypoxia-induced nucleophosmin protects cell death through inhibition of p53.
PG  - 41275-9
AB  - Nucleophosmin (NPM) is a multifunctional protein that is overexpressed in 
      actively proliferating cells and cancer cells. Here we report that this 
      proliferation-promoting protein is strongly induced in response to hypoxia in 
      human normal and cancer cells. Up-regulation of NPM is hypoxia-inducible factor-1 
      (HIF-1)-dependent. The NPM promoter encodes a functional HIF-1-responsive element 
      that can be activated by hypoxia or forced expression of HIF-1alpha. Suppression 
      of NPM expression by small interfering RNA targeting NPM increases 
      hypoxia-induced apoptosis, whereas overexpression of NPM protects against hypoxic 
      cell death of wild-type but not p53-null cells. Moreover, NPM inhibits 
      hypoxia-induced p53 phosphorylation at Ser-15 and interacts with p53 in hypoxic 
      cells. Thus, this study not only demonstrates hypoxia regulation of a 
      proliferation-promoting protein but also suggests that hypoxia-driven cancer 
      progression may require increased expression of NPM to suppress p53 activation 
      and maintain cell survival.
FAU - Li, June
AU  - Li J
AD  - Division of Experimental Hematology, Cincinnati Children's Hospital Medical 
      Center, Cincinnati, Ohio 45229, USA.
FAU - Zhang, Xiaoling
AU  - Zhang X
FAU - Sejas, Daniel P
AU  - Sejas DP
FAU - Bagby, Grover C
AU  - Bagby GC
FAU - Pang, Qishen
AU  - Pang Q
LA  - eng
GR  - R01 CA109641/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040813
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Nucleoplasmins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - *Apoptosis
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/physiology
MH  - Humans
MH  - Hypoxia/metabolism/*pathology
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Neoplasms/metabolism/pathology
MH  - Nuclear Proteins/biosynthesis/*physiology
MH  - Nucleoplasmins
MH  - Phosphoproteins/biosynthesis/*physiology
MH  - Phosphorylation
MH  - Promoter Regions, Genetic
MH  - Response Elements
MH  - Transcription Factors/physiology
MH  - Transcription, Genetic
MH  - Tumor Suppressor Protein p53/*antagonists & inhibitors/metabolism
MH  - *Up-Regulation
EDAT- 2004/08/18 05:00
MHDA- 2004/11/16 09:00
CRDT- 2004/08/18 05:00
PHST- 2004/08/18 05:00 [pubmed]
PHST- 2004/11/16 09:00 [medline]
PHST- 2004/08/18 05:00 [entrez]
AID - S0021-9258(20)72583-4 [pii]
AID - 10.1074/jbc.C400297200 [doi]
PST - ppublish
SO  - J Biol Chem. 2004 Oct 1;279(40):41275-9. doi: 10.1074/jbc.C400297200. Epub 2004 
      Aug 13.